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1. 发明授权

US09744188B2 Methods of promoting neuronal outgrowth by gypican 2 that binds to receptor protein tyrosine phosphatase sigma 有权
公开(公告)号：US09744188B2
公开(公告)日：2017-08-29
申请号：US13985629
申请日：2012-02-17
申请人： John G. Flanagan , Yingjie Shen , Edith Yvonne Jones , Alexandru Radu Aricescu , Charlotte Hannah Coles
发明人： John G. Flanagan , Yingjie Shen , Edith Yvonne Jones , Alexandru Radu Aricescu , Charlotte Hannah Coles
IPC分类号： A61K38/00 , A61K38/18 , A61K49/00 , C07K14/475 , C07K14/48 , C07K14/00 , A61K31/727 , A61K45/06 , A61K31/737 , A61K38/17
CPC分类号： A61K31/727 , A61K31/737 , A61K38/177 , A61K45/06 , A61K2300/00
摘要： Disclosed herein are methods of inducing neuronal outgrowth of a neuron. The methods comprise contacting the neuron with an agent that binds receptor protein tyrosine phosphatase δ (RPTPδ), to thereby induce neuronal outgrowth of the neuron. The agent may induces clustering of RPTPδ and/or inhibit binding of chondroitin sulfate proteoglycan (CSPG) to RPTPδ. Examples of suitable agents are heparan sulfate proteoglycan, heparan sulfate, heparan sulfate oligosaccharides, or heparin oligosaccharides. Additional agents are also disclosed. The neuron can be a CNS neuron or peripheral neuron. Also disclosed herein are methods of treating neuronal injury in a subject comprising, administering to the subject an agent that binds RPTPδ. Administration may be to a site of neuronal injury, to thereby induce neuronal outgrowth at the site of neuronal injury.

2. 发明申请

US20140045762A1 MOLECULAR SWITCH FOR NEURONAL OUTGROWTH 有权
标题翻译：分子开关用于神经生物学
公开(公告)号：US20140045762A1
公开(公告)日：2014-02-13
申请号：US13985629
申请日：2012-02-17
申请人： John G. Flanagan , Yingjie Shen , Edith Yvonne Jones , Alexandru Radu Aricescu , Charlotte Hannah Bonn
发明人： John G. Flanagan , Yingjie Shen , Edith Yvonne Jones , Alexandru Radu Aricescu , Charlotte Hannah Bonn
IPC分类号： A61K31/727 , A61K38/17
CPC分类号： A61K31/727 , A61K31/737 , A61K38/177 , A61K45/06 , A61K2300/00
摘要： Disclosed herein are methods of inducing neuronal outgrowth of a neuron. The methods comprise contacting the neuron with an agent that binds receptor protein tyrosine phosphatase δ (RPTPδ), to thereby induce neuronal outgrowth of the neuron. The agent may induces clustering of RPTPδ and/or inhibit binding of chondroitin sulfate proteoglycan (CSPG) to RPTPδ. Examples of suitable agents are heparan sulfate proteoglycan, heparan sulfate, heparan sulfate oligosaccharides, or heparin oligosaccharides. Additional agents are also disclosed. The neuron can be a CNS neuron or peripheral neuron. Also disclosed herein are methods of treating neuronal injury in a subject comprising, administering to the subject an agent that binds RPTPδ. Administration may be to a site of neuronal injury, to thereby induce neuronal outgrowth at the site of neuronal injury.
摘要翻译：本文公开了诱导神经元的神经元生长的方法。所述方法包括使神经元与结合受体蛋白酪氨酸磷酸酶δ（RPTPdelta）的试剂接触，从而诱导神经元的神经元生长。该试剂可诱导RPTPδ的聚集和/或抑制硫酸软骨素蛋白聚糖（CSPG）与RPTPδ的结合。合适的试剂的实例是硫酸乙酰肝素蛋白聚糖，硫酸乙酰肝素，硫酸乙酰肝素寡糖或肝素低聚糖。还公开了另外的试剂。神经元可以是CNS神经元或外周神经元。本文还公开了治疗受试者神经元损伤的方法，其包括向受试者施用结合RPTPδ的药剂。管理可能是神经元损伤的部位，从而在神经元损伤部位诱导神经元生长。

3. 发明申请

US20120231014A1 Neural Regeneration 审中-公开
标题翻译：神经再生
公开(公告)号：US20120231014A1
公开(公告)日：2012-09-13
申请号：US13391210
申请日：2010-08-18
申请人： John G. Flanagan , Alan Peter Tenney , Yingjie Shen , Jerry Silver
发明人： John G. Flanagan , Alan Peter Tenney , Yingjie Shen , Jerry Silver
IPC分类号： A61K39/395 , A61P25/00 , A61K38/46 , A61K38/17 , C12N5/0793 , C12N5/071
CPC分类号： A61K38/1709 , C07K2319/30
摘要： A method of promoting neural cell regeneration is carried out by contacting a neural cell with a compound that inhibits the binding of a chondroitin sulfate proteoglycan (CSPG) to a cellular (e.g., trans-membrane) PTPσ protein. The neural cell is associated with an injury or neurodegenerative condition.
摘要翻译：促进神经细胞再生的方法是通过使神经细胞与抑制硫酸软骨素蛋白聚糖（CSPG）与细胞（例如，跨膜）PTP的结合的化合物接触进行的。蛋白。神经细胞与损伤或神经变性疾病有关。

4. 发明授权

US06919313B2 Protein waving a PDZ and a RGS domain 失效
标题翻译：蛋白质挥发PDZ和RGS结构域
公开(公告)号：US06919313B2
公开(公告)日：2005-07-19
申请号：US10113794
申请日：2002-04-01
申请人： John G. Flanagan , Qiang Lu , Edna E. Sun
发明人： John G. Flanagan , Qiang Lu , Edna E. Sun
IPC分类号： C07K14/715 , C12N5/08 , G01N33/68 , A61K38/17 , C07K14/46
CPC分类号： G01N33/6872 , C07K14/7158 , G01N33/6869 , G01N2333/54 , G01N2333/715 , G01N2333/726 , G01N2500/02 , G01N2500/04
摘要： Transmembrane B ephrins and their Eph receptors signal hi-directionally. The presently claimed invention describes a cytoplasmic protein, designated PDZ-RGS3, which binds B ephrins through a PDZ domain, and has a regulator of heterotrimeric G protein signaling (RGS) domain. PDZ-RGS3 mediates signaling from the ephrin-B cytoplasmic tail. SDF-1, a chemokine with a G protein coupled receptor, or BDNF, act as chemoattractants for cerebellar granule cells, with SDF-1 action being selectively inhibited by soluble EphB receptor. The claimed invention reveals a pathway that links reverse signaling to cellular guidance, uncovers a novel mode of control for G proteins, and demonstrates a mechanism for selective regulation of responsiveness to neuronal guidance cues. Further, compositions and methods of use are provided for modulating cell migration as a function of chemokines and GPCR interaction, to aid in the treatment of disease states and medical conditions, including cancer and immune responses such as allergy and autoimmune responses. In one embodiment, a method of altering the sensitivity of a cell to a chemokine is provided using a PDZ-RGS3 protein.
摘要翻译：跨膜B ephrins及其Eph受体信号向高信号。目前要求保护的发明描述了称为PDZ-RGS3的细胞质蛋白，其通过PDZ结构域结合B ephrins，并具有异源三聚G蛋白信号传导（RGS）结构域的调节剂。 PDZ-RGS3介导ephrin-B细胞质尾巴的信号转导。具有G蛋白偶联受体的趋化因子SDF-1或BDNF作为小脑颗粒细胞的化学引诱物，SDF-1作用被可溶性EphB受体选择性抑制。所要求保护的发明揭示了将反向信号转导到细胞引导的途径，揭示了G蛋白的新型控制模式，并且展示了选择性调节对神经元指导线索的反应性的机制。此外，提供组合物和使用方法用于调节作为趋化因子和GPCR相互作用的功能的细胞迁移，以帮助治疗疾病状态和医学病症，包括癌症和免疫应答如过敏和自身免疫应答。在一个实施方案中，使用PDZ-RGS3蛋白提供了改变细胞对趋化因子的敏感性的方法。

5. 发明授权

US5801000A Detection and isolation of receptors 失效
标题翻译：受体的检测和分离
公开(公告)号：US5801000A
公开(公告)日：1998-09-01
申请号：US608688
申请日：1996-02-29
申请人： Philip Leder , John G. Flanagan
发明人： Philip Leder , John G. Flanagan
IPC分类号： A61K38/00 , C07K14/705 , C07K14/73 , C07K14/82 , C12N9/16 , G01N33/53 , G01N33/569 , G01N33/574 , G01N33/535 , G01N33/566
CPC分类号： G01N33/57492 , C07K14/705 , C07K14/70514 , C07K14/82 , C12N9/16 , G01N33/53 , G01N33/56988 , G01N33/5748 , A61K38/00 , C07K2319/00 , C07K2319/036 , C07K2319/32 , Y10S435/96 , Y10S435/963 , Y10S436/824
摘要： Disclosed is a method of isolating a ligand from a sample, the method including: providing a hybrid molecule including the receptor for the ligand covalently bonded to the first member of a specific binding pair; contacting sample with the hybrid molecule to form an affinity complex between the ligand and the hybrid molecule; and isolating the affinity complex using the second member of the specific binding pair. Also disclosed is a c-kit ligand, nucleic acid encoding such a ligand, and recombinant cells containing such nucleic acid. The c-kit ligand may be used to stimulate hematopoietic cell growth.
摘要翻译：公开了从样品中分离配体的方法，所述方法包括：提供包含共价键合到特异性结合对的第一个成员的配体的受体的杂合分子; 使样品与杂交分子接触以在配体和杂交分子之间形成亲和复合物; 并使用特异性结合对的第二个成员分离亲和复合体。还公开了c-kit配体，编码这种配体的核酸和含有该核酸的重组细胞。 c-kit配体可用于刺激造血细胞生长。

6. 发明授权

US06399326B1 Nucleic acids encoding neural/pancreatic receptor tyrosine phosphatase 失效
标题翻译：编码神经/胰腺受体酪氨酸磷酸酶的核酸
公开(公告)号：US06399326B1
公开(公告)日：2002-06-04
申请号：US08884569
申请日：1997-06-27
申请人： Ming-Ko Chiang , John G. Flanagan
发明人： Ming-Ko Chiang , John G. Flanagan
IPC分类号： C12P2106
CPC分类号： C12Q1/6883 , A01K2217/05 , A01K2217/075 , A61K38/00 , A61K39/00 , C12N9/16 , C12Q2600/158
摘要： We describe here a new class of protein tyrosine phosphatases (PTP), called “PTP-NP” (for neural and pancreatic) receptors. The sequence of an exemplary PTP-NP gene (SEQ ID No. 1) indicates it encodes a receptor type PTP (SEQ ID No. 2) with a single tyrosine phosphatase domain. Comparison of PTP-NP with the other known PTPs reveals a cysteine-conserved motif in the extracellular domain and, together with their homology in the phosphatase domain, this defines a new subclass of receptor type PTPs.
摘要翻译：我们在这里描述了一类新的蛋白酪氨酸磷酸酶（PTP），称为“PTP-NP”（用于神经和胰腺）受体。示例性PTP-NP基因（SEQ ID No.1）的序列表示它用单个酪氨酸磷酸酶结构域编码受体型PTP（SEQ ID No.2）。 PTP-NP与其他已知PTPs的比较揭示了细胞外结构域中的半胱氨酸保守基序，并且与磷酸酶结构域中的同源性一起定义了受体型PTP的新亚类。

7. 发明授权

US5789182A System for assaying binding to a heparin-binding growth factor receptor 失效
标题翻译：用于测定与肝素结合生长因子受体结合的系统
公开(公告)号：US5789182A
公开(公告)日：1998-08-04
申请号：US166717
申请日：1993-12-14
申请人： Avner Yayon , David M. Ornitz , Michael Klagsbrun , Philip Leder , John G. Flanagan
发明人： Avner Yayon , David M. Ornitz , Michael Klagsbrun , Philip Leder , John G. Flanagan
IPC分类号： C07K14/50 , C07K14/71 , C12N9/16 , G01N33/50 , G01N33/74 , C12Q1/00 , C12N15/09
CPC分类号： G01N33/5008 , C07K14/503 , C07K14/71 , C12N9/16 , G01N33/74 , C07K2319/034 , C07K2319/32 , C07K2319/61 , G01N2500/00
摘要： A homogeneous population of cells having on average (1) a number of cell surface low-affinity heparin-binding growth factor (HBGF) sites per cell less than 20% of the number of such binding sites found on wild-type CHO-K1 cells (ATCC Accession No. CCL61), and at least three times the number of cell surface high-affinity HBGF receptors per cell found on such CHO-K1 cells; and an assay system utilizing such cells.
摘要翻译：平均每个细胞的细胞表面平均少量细胞表面低亲和力肝素结合生长因子（HBGF）位点的均匀群体少于在野生型CHO-K1细胞上发现的这种结合位点数目的20％（ATCC登录号CCL61），并且在这种CHO-K1细胞上发现的每个细胞的细胞表面高亲和力HBGF受体的数目的至少三倍; 以及利用这种细胞的测定系统。

8. 发明授权

US06777536B1 EPH receptor ligands, and uses related thereto 失效
标题翻译： EPH受体配体及其用途
公开(公告)号：US06777536B1
公开(公告)日：2004-08-17
申请号：US08393462
申请日：1995-02-27
申请人： John G. Flanagan , Hwai-Jong Cheng
发明人： John G. Flanagan , Hwai-Jong Cheng
IPC分类号： C07K1400
CPC分类号： C07K14/52 , A01K2217/05 , A61K38/00 , C07K2319/00 , C12N2799/021
摘要： The present invention relates to the discovery of a novel EPH receptor ligand, referred to hereinafter as “Elf-1”, which protein has apparently broad involvement in the formation and maintenance of ordered spatial arrangements of differentiated tissues in vertebrates, and can be used to generate and/or maintain an array of different vertebrate tissue both in vitro and in vivo.
摘要翻译：本发明涉及一种新型EPH受体配体的发现，该配体在下文称为“Elf-1”，该蛋白质明显地涉及脊椎动物中分化组织的有序空间排列的形成和维持，并且可用于在体外和体内产生和/或维持不同脊椎动物组织的阵列。

9. 发明授权

US5795734A EPH receptor ligands, and uses related thereto 失效
公开(公告)号：US5795734A
公开(公告)日：1998-08-18
申请号：US455001
申请日：1995-05-31
申请人： John G. Flanagan , Hwai-Jong Cheng
发明人： John G. Flanagan , Hwai-Jong Cheng
IPC分类号： A61K38/00 , C07K14/52 , C12N15/12
CPC分类号： C07K14/52 , A01K2217/05 , A61K38/00 , C07K2319/00 , C12N2799/021
摘要： The present invention relates to the discovery of a novel EPH receptor ligand, referred to hereinafter as "Elf-1", which protein has apparently broad involvement in the formation and maintenance of ordered spatial arrangements of differentiated tissues in vertebrates, and can be used to generate and/or maintain an array of different vertebrate tissue both in vitro and in vivo.

10. 发明授权

US5554499A Detection and isolation of ligands 失效
标题翻译：配体的检测和分离
公开(公告)号：US5554499A
公开(公告)日：1996-09-10
申请号：US306255
申请日：1994-09-14
申请人： Philip Leder , John G. Flanagan
发明人： Philip Leder , John G. Flanagan
IPC分类号： A61K38/00 , C07K14/705 , C07K14/73 , C07K14/82 , C12N9/16 , G01N33/53 , G01N33/569 , G01N33/574 , G01N33/535 , G01N33/566
CPC分类号： G01N33/57492 , C07K14/705 , C07K14/70514 , C07K14/82 , C12N9/16 , G01N33/53 , G01N33/56988 , G01N33/5748 , A61K38/00 , C07K2319/00 , C07K2319/036 , C07K2319/32 , Y10S435/96 , Y10S435/963 , Y10S436/824
摘要： Disclosed is a method of isolating a ligand from a sample, the method including: providing a hybrid molecule including the receptor for the ligand covalently bonded to the first member of a specific binding pair; contacting sample with the hybrid molecule to form an affinity complex between the ligand and the hybrid molecule; and isolating the affinity complex using the second member of the specific binding pair. Also disclosed is a c-kit ligand, nucleic acid encoding such a ligand, and recombinant cells containing such nucleic acid. The c-kit ligand may be used to stimulate hematopoietic cell growth.
摘要翻译：公开了从样品中分离配体的方法，所述方法包括：提供包含共价键合到特异性结合对的第一个成员的配体的受体的杂合分子; 使样品与杂交分子接触以在配体和杂交分子之间形成亲和复合物; 并使用特异性结合对的第二个成员分离亲和复合体。还公开了c-kit配体，编码这种配体的核酸和含有该核酸的重组细胞。 c-kit配体可用于刺激造血细胞生长。

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